Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001127 (respiratory acidosis)
 1,501 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A kidney epithelial cell line, LLC-PK1, which does not synthesize prostaglandins, provides an ideal in vitro model system to investigate the effect of prostaglandins in the regulation of renal ammoniagenesis. Previous studies from our laboratory have demonstrated significant increases in glutamine-dependent ammonia and alanine production by rocked cultures of LLC-PK1 cells subjected to either acute metabolic or respiratory acidosis. In the study presented here, experiments were conducted to investigate the role of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) in the response of ammonia metabolism to acute metabolic acidosis by LLC-PK1 cells. A low dose of PGF2 alpha (0.1 ng/mL) dramatically inhibited the stimulatory effect of a low pH (pH 6.8) on ammonia production. In contrast, the inhibition of cytosolically generated alanine was less dramatic and averaged only 20% of the effect on ammonia production. Furthermore, PGF2 alpha increased cellular alpha-ketoglutarate concentration, suggesting an increase in intramitochondrial pH. Thus, the cellular mechanism of PGF2 alpha action appears to involve either interference with the cytosolic pH signal or its translation to the intramitochondrial compartment. The inhibitory response of PGF2 alpha on pH-stimulated ammoniagenesis was progressively lost at higher concentrations. Both low-dose (0.1 ng/mL) and high-dose (10 ng/mL) PGF2 alpha had no significant effect on the basal rates of ammonia and alanine production at pH 7.4. PGE2, on the other hand, did not exhibit any significant response on ammonia or alanine production at either pH 6.8 or 7.4 when given in a wide range of doses.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prostaglandin F2 alpha inhibits the ammoniagenic response to acute acidosis in LLC-PK1 cells. 210 48

The effects of acid-base balance disturbances on pulmonary endothelial angiotensin-converting enzyme (ACE) were studied in anesthetized mechanically ventilated rabbits. Enzyme function was estimated from [3H]benzoyl-Phe-Ala-Pro ([3H]BPAP) utilization under first-order reaction conditions during a single transpulmonary passage and expressed as 1) substrate metabolism (M), 2) Amax/Km (Amax being equal to the product of enzyme mass and the constant of product formation), and 3) (Amax/Km)/100 ml blood flow. When respiratory acidosis/alkalosis was produced by altering respiratory rate at constant airway pressure, substrate (BPAP) utilization varied proportionally to arterial pH and inversely proportionally to arterial PCO2 (PaCO2) (P less than 0.05). Percent BPAP metabolism (%M) ranged from 92 +/- 3 (respiratory alkalosis) to 85 +/- 3 (normal), 82 +/- 3 (respiratory acidosis), and 78 +/- 2% (severe respiratory acidosis). Amax/Km similarly decreased from 899 +/- 129 to 825 +/- 143, 601 +/- 74, and 450 +/- 34 ml/min, respectively, and (Amax/Km)/100 ml blood flow was reduced from 176 +/- 26 to 131 +/- 22, 111 +/- 12, and 97 +/- 5, respectively. However, when respiratory acidosis/alkalosis was produced by altering both respiratory rate and airway pressure, no changes were observed in either %M, Amax/Km or (Amax/Km)/100 ml blood flow. Similarly metabolic alkalosis or acidosis did not alter M, Amax/Km or (Amax/Km)/100 ml blood flow. These results indicate that pulmonary endothelial ACE function can be affected by acid-base disturbances, probably indirectly through changes in perfused microvascular surface area.
 ...
PMID:Effects of acid-base imbalance on pulmonary angiotensin-converting enzyme in vivo. 282 79

Despite the potential utility of endothelial metabolic substrates for the early clinical detection of acute lung injury, the relationship between lung capillary injury and pulmonary endothelial metabolic function remains incompletely understood. Previous studies have shown that lung capillaries are damaged by oxygen toxicity in the sheep; however, metabolic functions of the pulmonary endothelium have not been examined in this otherwise well-characterized animal model of lung injury. Therefore, we studied the activity of pulmonary endothelial angiotensin-converting enzyme (ACE) in five unanesthetized adult sheep that breathed 100% O2 via tracheostomy for 3 days and in four other sheep that breathed compressed air. In contrast to the sheep that breathed air, the sheep that breathed O2 developed substantial arterial hypoxemia and hypercapnia, an increased alveolar-to-arterial O2 gradient and a slight respiratory acidosis. Morphological examination of lungs from sheep that breathed O2 revealed a multifocal distribution of injury, including interstitial edema, capillary endothelial damage, and alveolar epithelial damage. Indicator-dilution methods were used to assess first-pass pulmonary metabolism of the ACE substrate [3H]Benzoyl-Phe-Ala-Pro (BPAP) and the apparent kinetics (KM and Vmax) of ACE activity. Pulmonary metabolism of BPAP exhibited saturability, was reduced by an ACE inhibitor (enalaprit), and did not result from the activity of circulating plasma ACE. There was no difference between the 2 groups of sheep in the percent metabolism of either 0.1 mumol BPAP/kg or 1.0 mumol BPAP/kg or in the KM of BPAP metabolism. In both groups, the Vmax and Vmax/KM decreased as a result of reductions in cardiac output and volume distribution.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Pulmonary angiotensin-converting enzyme activity in the oxygen-toxic sheep. 284 37

Glucose metabolites (lactate, pyruvate, citrate, malate), alanine, glutamate and adenosine triphosphate (ATP) were determined in the resting anterior tibial muscle of dogs. The muscle was sampled in anesthetized animals first breathing air, and secondly after an hour of breathing a hypercapnic mixture, FICO2 = 0.10 (experimental subjects n = 6) or air (control subjects n = 6). A decrease in concentration of glucose metabolites (lactate: -34%; pyruvate: -24%; Citrate: -34%; malate: -54%), glutamate (-43%), alanine (-35%) and ATP (-8%) was observed in the resting muscle during acute hypercapnic acidosis. This was not the case in control animals breathing air.
 ...
PMID:Resting muscle glucose metabolites and related compounds in hypercapnia. 369 95

In vivo the dog kidney responds to metabolic or respiratory acidosis by a marked increment of its ammonia production (expressed per 100 milliliters glomerular filtration rate). This phenomenon is related to a switch from metabolic utilization of nonammoniagenic (lactate) to ammoniagenic (glutamine) substrates to support ATP turnover in the proximal tubules. We have proposed that in vivo the maximum activity of the ammoniagenic process is fixed by the ATP turnover in this segment of the nephron. The maximal glutamine metabolism is reached when 100% of this turnover is supported by glutamine metabolism. We have studied how these concepts apply to the adaptation of glutamine metabolism and ammonia production to a low pH in vitro using proximal tubules of dogs incubated when one (lactate or glutamine) or several (glutamine plus lactate or plus palmitate) substrates are provided. At pH 7.4 glutamine alone supports already 71-76% of the tissue ATP turnover (minimal and maximal values). With acidification this fraction rises to nearly 87-94%, but this increases only modestly the ammonia production. Reducing the ATP turnover with ouabain at pH 7.4 decreases the absolute glutamine utilization, which now supports only 45-50% of the ATP turnover. Again acidification increases this fraction to 90-99%. Addition of lactate with glutamine displaces part of the glutamine metabolized, but greatly stimulates the synthesis of alanine. Fatty acids depress ammonia production and blunt the tissue response to acidification. Gluconeogenesis from lactate is minimally influenced by incubation pH. It is concluded that the ATP turnover limits the metabolism of glutamine by proximal tubules in vitro as in vivo in the dog, and that the response to acidification is small in vitro because of the absence of alternative substrates.
 ...
PMID:ATP turnover and renal response of dog tubules to pH changes in vitro. 377 88

The effects of acute hypoxemia and hypercapnic acidosis were examined in five unanesthetized dogs in which sodium intake was controlled at 80 mEq/24 hours for 4 days prior to study. Each animal was studied during combined acute hypoxemia and hypercapnic acidosis (Pao2 = 36 +/- 1 mm Hg, Paco2 = 52 +/- 1 mm Hg, pH = 7.18 +/- 0.02), acute hypoxemia alone (Pao2 = 32 +/- 1 mm Hg, Paco2 = 32 +/- 1mm Hg, pH = 7.34 +/- 0.01), and acute hypercapnic acidosis alone (Pao2 = 82 +/- 2 mm Hg, Paco2 = 51 +/- 1 mm Hg, pH = 7.18 +/- 0.02). Although mean arterial pressure, cardiac output, and heart rate increased during combined hypoxemia and hypercapnic acidosis, effective renal plasma flow and glomerular filtration rate decreased. In addition, filtered sodium load and urinary sodium excretion decreased during combined hypoxemia and hypercapnic acidosis. Either acute hypoxemia or hypercapnic acidosis alone resulted in increased mean arterial pressure, cardiac output, and heart rate. However, in contrast to their combined effects, renal hemodynamic function was unchanged and natriuresis was observed. Measurement of plasma renin activity and angiotensin II concentrations indicated that hypoxemia or hypercapnic acidosis alone resulted in moderate activation of the renin-angiotensin system. Moreover, combined hypoxemia and hypercapnic acidosis acted synergistically resulting in major renin-angiotensin activation. Systemic angiotensin II blockade using 1-sarcosine, 8-alanine, angiotensin II (2 micrograms/kg per min) during combined acute hypoxemia and hypercapnic acidosis resulted in decreased renal hemodynamic function. We conclude that acute hypoxemia and hypercapnic acidosis act synergistically to increase mean arterial pressure, diminish renal hemodynamic function and activate the renin-angiotensin system. Systemic angiotensin inhibition studies suggest activation of the renin-angiotensin system maintains renal hemodynamic function during combined hypoxemia and hypercapnic acidosis, instead of mediating the renal vasoconstriction.
 ...
PMID:Synergistic effects of acute hypoxemia and hypercapnic acidosis in conscious dogs. Renal dysfunction and activation of the renin-angiotensin system. 641 80

The physiological relationship of increased circulating angiotensin II and vasopressin to circulatory changes during combined hypoxemia and hypercapnic acidosis is unclear. To evaluate the role(s) of angiotensin II and vasopressin, seven unanesthetized female mongrel dogs with controlled sodium intake (80 meq/24 h X 4 d) were studied during 40 min of combined acute hypoxemia and hypercapnic acidosis (PaO2, 36 +/- 1 mmHg; PaCO2, 55 +/- 2 mmHg; pH = 7.16 +/- 0.04) under the following conditions: (a) intact state with infusion of vehicles alone; (b) beta-adrenergic blockade with infusion of d,l-propranolol (1.0 mg/kg bolus, 0.5 mg/kg per h); of the vasopressin pressor antagonist d-(CH2)5Tyr(methyl)arginine-vasopressin (10 micrograms/kg); and (d) simultaneous vasopressin pressor and angiotensin II inhibition with the additional infusion of 1-sarcosine, 8-alanine angiotensin II (2.0 micrograms/kg per min). The rise in mean arterial pressure during the combined blood-gas derangement with vehicles appeared to be related to increased cardiac output, since total peripheral resistance fell. Beta-adrenergic blockade abolished the fall in total peripheral resistance and diminished the rise in cardiac output during combined hypoxemia and hypercapnic acidosis, but the systemic pressor response was unchanged. In addition, the rise in mean arterial pressure during the combined blood-gas derangement was unaltered with vasopressin pressor antagonism alone. In contrast, the simultaneous administration of the vasopressin pressor and angiotensin II inhibitors during combined hypoxemia and hypercapnic acidosis resulted in the abrogation of the overall systemic pressor response despite increased cardiac output, owing to a more pronounced fall in total peripheral resistance. Circulating catecholamines were increased during the combined blood-gas derangement with vasopressin pressor and angiotensin II blockade, suggesting that the abolition of the systemic pressor response in the last 30 min of combined hypoxemia and hypercapnic acidosis was not related to diminished activity of the sympathetic nervous system. These studies show that vasopressin and angiotensin II are major contributors to the systemic pressor response during combined acute hypoxemia and hypercapnic acidosis.
 ...
PMID:Role of arginine vasopressin and angiotensin II in cardiovascular responses to combined acute hypoxemia and hypercapnic acidosis in conscious dogs. 654 29

Five healthy males took part in two separate studies. In one study subjects breathed air (control, C) and in the other 5% CO2 in 21% O2 (respiratory acidosis, RA). Measurements were made at rest, during exercise at 30 and 60% maximal O2 uptake (VO2 max), (20 min each) and in recovery. RA was associated with higher arterial CO2 partial pressure (PCO2) and bicarbonate and lower pH than C. The increase with exercise in plasma lactate (mmol . l-1) was less in RA than C from 1.0 +/- 0.15 (SE) (C = 1.1 +/- 0.17) at rest to 5.3 +/- 1.25 (C = 6.8 +/- 0.98) at 60% VO2 max (P less than 0.10). Plasma pyruvate, alanine, and glycerol concentrations increased with exercise; free fatty acids did not change. There were no significant differences between RA and C in any of these metabolites. Norepinephrine concentrations were similar at rest but increased to a greater extent during exercise in RA than C (P less than 0.02). Epinephrine levels were also higher in RA than C at 60% VO2 max (NS); the two subjects in whom lactate was not lower with RA showed the greatest increase in epinephrine. Exercise in RA was associated with higher heart rates (P less than 0.05), blood pressures (NS), and ventilation (P less than 0.01). In hypercapnia the metabolic effects of acidosis are modified by increased levels of circulating catecholamines.
 ...
PMID:Effect of respiratory acidosis on metabolism in exercise. 681 26

The rate of net glutamine degradation in non-recirculating perfused rat liver was estimated by the release of urea, ammonia and alanine in steady states of operation of glutaminase. Corrected for a slight intracellular accumulation of glutamate, accounting for 7% of the flux at 5mM glutamine, the estimated glutaminase activity agrees well with measurements of glutamine removal described in the literature for recirculating perfusion experiments. Glutaminase activity was decreased when the perfusate pH was lowered (i) by infusion of hydrochloric acid, (ii) by increasing the CO2 concentration, or (iii) by decreasing the hydrogencarbonate concentration. Conversely, it was increased when the perfusate pH was increased by infusion of sodium hydroxide or by increasing the hydrogencarbonate concentration. However, glutaminase activity did not depend on medium hydrogencarbonate. When the hydrogencarbonate buffer system was replaced by DMO or by Hepes equilibrated with O2 (no CO2 present), there was practically no change in the observed rates. These results, obtained in an iso-pH system, are in contrast to recent suggestions of a role of hydrogencarbonate in the regulation of glutamine metabolism based on results from incubations of isolated mitochondria or hepatocytes. It is concluded that the conservation of glutamine by the inhibition of hepatic glutaminase, which provides glutamine for the pH regulation by renal glutaminase, can be increased not only in metabolic acidosis but also in respiratory acidosis associated with high hydrogencarbonate concentration.
 ...
PMID:The role of pH and the lack of a requirement for hydorgencarbonate in the regulation of hepatic glutamine metabolism. 740 50

The acid-base status of extra- and intracellular fluids was studied in relation to the anaerobic energy metabolism in the adductor muscle, mantle, gills, and heart of the marine bivalve Crassostrea gigas after exposure to air for periods of 2, 4, 8, 12, 24, and 48 h. Such exposure was found to cause a significant reduction in the pH in the hemolymph (pH(e)) within the first 4 h. The decrease in the pHe was accompanied by elevated Pco2 values, causing [HCO3-] to rise (respiratory acidosis). Thereafter, the pHe fell at a lower rate, and this fall was partially compensated for by a further increase in [HCO3-] in the hemolymph. The increase in the [Ca] levels in the hemolymph indicates a mobilization of Ca2+ from CaCO3 and the involvement of bicarbonates in the buffering of pHe. The main anaerobic end-products that accumulated in the tissues during the first stages of anaerobiosis were alanine and succinate, at a ratio of about 2 : 1. Later on, propionate and acetate were also accumulated at significant rates. In contrast to the adductor muscle, gills, and mantle, opine production in the heart was significant after 12-24 h of exposure to air. Determination of intracellular pH (pHi) revealed that there is a close relationship between the rate of anaerobic end-product accumulation and the extent of intracellular acidosis in the adductor muscle, mantle, and gills. On the contrary, accumulation of anaerobic end-products in the heart did not cause any significant change in its pHi. The intracellular nonbicarbonate, nonphosphate buffering value (beta (NB,NPi)) was determined to be higher in the heart than in the other three tissues and thus probably plays a crucial role in stabilizing heart pHi during exposure to air.
 ...
PMID:Extracellular and intracellular acid-base status with regard to the energy metabolism in the oyster Crassostrea gigas during exposure to air. 1588 84


1 2 Next >>